Traitement des carcinoses péritonéales d'origine colo-rectale. Quoi ...

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Original Article Toward Curative Treatment of Peritoneal Carcinomatosis From Nonovarian Origin by Cytoreductive Surgery Combined With Perioperative Intraperitoneal Chemotherapy A Multi-Institutional Study of 1290 Patients Olivier Glehen, MD, PhD 1 ; François N. Gilly, MD, PHD 1 ; Florent Boutitie 2 ; Jean M. Bereder, MD 3 ; François Quenet, MD 4 ; Lucas Sideris, MD 5 ; Baudouin Mansvelt, MD 6 ;Gérard Lorimier, MD 7 ; Simon Msika, MD, PhD 8 ; Dominique Elias, MD, PhD 9 ; and the French Surgical Association BACKGROUND: Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival. METHODS: A retrospective, multicenter cohort study was performed in French-speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies. RESULTS: The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N ¼ 523), pseudomyxoma peritonei (N ¼ 301), gastric adenocarcinoma (N ¼ 159), peritoneal mesothelioma (N ¼ 88), and appendiceal adenocarcinoma (N ¼ 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement. CONCLUSIONS: A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long-term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC. Cancer 2010;116:5608–18. VC 2010 American Cancer Society. KEYWORDS: peritoneal carcinomatosis, intraperitoneal chemotherapy, hyperthermia, cytoreductive surgery, peritonectomy. Corresponding author: Olivier Glehen, MD, PhD, Surgical Oncology Department, Centre Hospitalo-Universitaire Lyon Sud, 69495, Pierre Bénite Cedex, France; Fax: (011) 33-478-863-343; olivier.glehen@chu-lyon.fr 1 2 Surgical Oncology Department, Lyon Civil Hospices, South Lyon University Hospital Center, Lyon, France; Biostatistics Service, Lyon Civil Hospices, Lyon, France; 3 4 Surgical Oncology Department, l’Archet Hospital, Nice University Hospital Center, Nice, France; Surgical Oncology Department, Val d’Aurelle Center, Montpellier, France; 5 Surgical Oncology Department, Maisonneuve-Rosemont Hospital, Montreal, Canada; 6 Surgical Oncology Department, Jolimont Hospital, Haine St. Paul, Belgium; 7 Surgical Oncology Department, Paul Papin Center, Angers, France; 8 Surgical Oncology Department, Louis Mourier Hospital, Collombes, France; 9 Surgical Oncology Department, Institut Gustave Roussy, Villejuif, France We acknowledge Faheez Mohamed for help with English editing, Nadine Bossard for statistical analysis, and other authors of the Association Française de Chirurgie (Abboud Karine, Bellevue Hospital, St. Etienne, France; Turrini Olivier, Padi Calmetteo Centre, Marseilles, France; Arvieux Catherine, Michallon Hospital, Grenoble, France; Rat Patrick, Bocage Hospital, Dijon, France; Gertsch Philippe, San Giovanni Hospital, Bellinzana, Switzerland; Ferron Gwenael, Claudias Regaud Centre, Toulouse, France; Meeus Pierre, Leon Berard Center, Lyon, France; Brigand Cécile, Hautepierre Hospital, Strausbourg, France; Marchal Frederic, Alexis Vautrin Center, Nancy, France; Tuech Jean Jacques, Charles Nicolle Hospital, Rouen, France; Pocard Marc, Lariboisiére Hospital, Paris, France; Loungnarath Rasmy, Saint Luc Hospital, Montreal, Canada; Saint Luc Hospital, Montreal, Canada; Tasseti Vincent, Emile Muller Hospital, Mulhouse, France; Lermite Emily, Angers Hospital, Angers, France; Durand Sylvaine, Dupuytren Hospital, Limoges, France; Van der Speeten Kurt, Ziekenhuis Oost-Limburg, Genk, Belgium). DOI: 10.1002/cncr.25356, Received: August 17, 2009; Revised: November 14, 2009; Accepted: December 28, 2009, Published online August 24, 2010 in Wiley Online Library (wileyonlinelibrary.com) 5608 Cancer December 15, 2010
The primary peritoneal malignancies, such as peritoneal mesothelioma or papillary serous carcinoma, are rare. In contrast, peritoneal dissemination from digestive cancers is common. In the past, carcinomatosis was regarded as a terminal disease, and most oncologists viewed it as a condition only to be palliated. However, recent reports describe curative treatment options for selected patients with carcinomatosis from nongynecologic cancer. 1-5 Over the past 2 decades, novel therapeutic approaches to peritoneal carcinomatosis (PC) have emerged that combine cytoreductive surgery and peritonectomy procedures 6 with perioperative intraperitoneal chemotherapy (PIC), including hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC). 7-9 Theoretically, cytoreductive surgery is performed to treat macroscopic disease, and PIC is used to treat microscopic residual disease with the objective of removing disease completely in a single procedure. Many consider it the standard of care for diseases like pseudomyxoma peritonei or peritoneal mesothelioma. 2,5,10 Moreover, it is the only plan that has produced curative results for carcinomatosis in international registries, 11 in several phase 2 trials, and in 1 phase 3 trial. 3,12-14 Despite all of these studies suggesting a survival benefit, oncologists remain skeptical regarding this combined therapeutic approach partly because of its perceived high toxicity. A collaborative effort of 25 French-speaking institutions involved in the treatment of peritoneal surface malignancies was performed on a large number of patients with PC from nongynecologic carcinomatosis to evaluate the tolerance and the efficacy of this Treatment of Peritoneal Carcinomatosis/Glehen et al treatment, to answer questions regarding patient selection, and to identify principal prognostic indicators. MATERIALS AND METHODS Patient Population One thousand two hundred ninety patients who had undergone 1344 procedures combining cytoreductive surgery and PIC for the treatment of PC from nonovarian origin between February 1989 and December 2007 made up the study population. The inclusion criteria were primary PC or PC of nonovarian origin confirmed by pathologic examination with HIPEC, EPIC, or both administered within 7 days of surgery. The exclusion criteria were PIC performed >7 days after the surgery and the presence of extra-abdominal metastases. Standardized clinical data on consecutive patients from each of 25 institutions involved in the management of peritoneal surface malignancies (France, 20 institutions; Belgium, 2 institutions; Quebec, Canada, 2 institutions; and Switzerland, 1 institution) were received and entered into a central database. Institutions provided data on between 1 and 400 patients. Figure 1 lists the periods during which patients were studied. The same author reviewed all data sheets before their entry into the database in an effort to make this a uniform interpretation of retrospective data. Data Forms A standard data form was created to retrieve information on the origin of PC and the status of the patient before undergoing the combined procedure, including age, sex, Figure 1. This chart illustrates the evolution of 1 year’s inclusions of procedures combining cytoreductive surgery and perioperative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis. Cancer December 15, 2010 5609
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